Introduction

Each year, CDER approves hundreds of new medications, most of which are variations of previously existing products, such as important new dosage forms of already-approved products, or cost-saving generic formulations. These new products contribute to quality of care, greater access to medication, more consumer choice, and a competitive marketplace that enhances affordability and public health. However, products in a small subset of these new approvals, that we refer to as novel drugs, are among the more truly innovative products that often help advance clinical care to another level. At the end of each calendar year, CDER summarizes these new products.

Our annual summary reports the quantity of novel drugs that we approved. However, we also focus on the quality of many of these new drugs, their contributions to enhanced patient care, and the various regulatory tools CDER used to help ensure their safe and efficient development and approval.

This year’s field of novel drugs will offer much to patients in need. We approved many new drugs to treat various forms of cancer, including four to treat multiple myeloma, and others to treat lung, skin, breast, brain, colorectal, and other cancers. This year’s field also includes new drugs to treat heart failure and high cholesterol, as well as the first approved reversal agent for a commonly-used blood thinner. We also approved new drugs for the treatment of patients with cystic fibrosis, and irritable bowel syndrome. In the area of infectious disease, our approvals include new treatments for urinary tract infections and chronic hepatitis C. For the second consecutive year, we approved more “orphan” drugs for rare diseases than any previous year in our history.

This work in effectively reviewing and approving new drugs is meaningful to the extent that we can also effectively ensure their safety. All of these newly approved products were required to meet our rigorous premarket safety standards --- and they will all be part of a strong postmarket safety surveillance system watching how they perform after they are more widely used by larger patient populations. We will summarize our safety activities in a different report.

We hope this summary provides an appreciation of the expected impact that many of the novel drug approvals of 2015 will have on patient care, as well as the valuable role CDER played in helping to bring these drugs to market.

Janet Woodcock, M.D.Director, Center for Drug Evaluation and Research

CDER’s 2015 Novel Drugs

45 novel drugs

In calendar year 2015, FDA’s Center for Drug Evaluation and Research (CDER) approved 45 novel drugs, approved as new molecular entities (NMEs) under New Drug Applications (NDAs) or as new therapeutic biologics under Biologics License Applications (BLAs).

Novel drugs are often innovative products that serve previously unmet medical needs or otherwise significantly help to advance patient care and public health. NMEs have chemical structures that have never been approved before. However, in some cases an NME may have actions similar to earlier drugs and may not necessarily offer unique clinical advantages over existing therapies. This report summarizes all of the 2015 NME and novel BLA approvals, emphasizing those that offer new and innovative treatments to patients in need.

The vertical bars in the graph below indicate the number of novel drugs approved by CDER in each year of the past decade. CDER approved 45 novel drugs in 2015. From 2006 through 2014, CDER has averaged about 28 novel drug approvals per year.

Applications for new approvals remain steady

CDER approved a higher than average number of novel drugs in 2015; however, the number of applications for these drugs that sponsors have submitted over time has remained relatively stable.

The points connected by lines in the graph below indicate the number of new NDA and BLA applications for new molecular entities and new therapeutic biologics CDER has received and filed for approval during the last 10 years. From 2006 through 2014, CDER filed an average of about 35 applications for novel drugs per year. CDER estimates 40 filings for 2015, which is consistent with previous years in this decade.

* This information is accurate as of December 31, 2015. In rare instances, it may be necessary for FDA to change a drug’s new molecular entity (NME) designation or the status of its application as a novel biologics license application (BLA). For instance, new information may become available which could lead to a reconsideration of the original designation or status. If changes must be made to a drug’s designation or the status of an application as a novel BLA, the Agency intends to communicate the nature of, and the reason for, any revisions as appropriate.

In 2015 CDER approved 45 novel drugs

45 novel drug approvals in CY 2015 is more than the average number approved annually during the past decade

From 2006 through 2014 CDER averaged about 28 novel drug approvals per year

*The 2015 filed numbers include those filed in CY 2015 plus those currently pending filing (i.e., within their 60 day filing period) in CY 2015.- Receipts that received a “Refuse to File” (RTF) or “Withdrawn before filing” (WF) identifier are excluded. - Multiple submissions (multiple or split originals) pertaining to a single new molecular/biologic entity are only counted once. - The filed number is not indicative of workload in the PDUFA V Program.

Impact

Impact on Public Health

Many of the 45 novel drugs CDER approved in 2015 are notable for their potential positive impact and unique contributions to quality medical care and public health.

First-in-Class

CDER identified 16 of the 45 novel drugs approved in 2015 (36%) as First-in-Class, one indicator of the innovative nature of a drug. These drugs often have mechanisms of action different from those of existing therapies. This First-in-Class approval rate is one factor that suggests the 2015 group of novel approvals is a field comprised of many innovative products.

Drugs for Rare Diseases

About 47% of the novel drugs approved in 2015 (21 of 45) were approved to treat rare or “orphan” diseases that affect 200,000 or fewer Americans. This is significant because patients with rare diseases often have few or no drugs available to treat their conditions.

Notable Novel Drugs of 2015: Another strong year for quality

In addition to the noteworthy examples of innovative First-in-Class and “orphan” new products mentioned previously above, the 2015 novel drug field also includes a variety of other notable drugs. These include the antibacterial drug Avycaz, to treat complicated intra-abdominal infections and complicated urinary tract infections, and the antifungal product Cresemba, to treat invasive aspergillosis and invasive mucormycosis, rare but serious infections. Also, the heart drugs, Entresto, to treat heart failure, and Corlanor, to reduce hospitalization from worsening heart failure; and the hypercholesterolemia (high cholesterol) treatments, Praluent, to treat certain patients with hard to treat heterozygous familial hypercholesterolemia and Repatha, to treat this same condition as well as homozygous familial hypercholesterolemia (a rare disease).

The year’s notable approvals also include Viberzi, to treat patients who have irritable bowel syndrome with diarrhea (IBS-D), Veltassa, to treat hyperkalemia (elevated potassium in the blood), and Daklinza, to treat chronic hepatitis C virus genotype 3 infections.

INNOVATION

Methods for expediting innovative novel drugs to market

CDER used a number of regulatory methods to expedite the development and approval of novel drugs in 2015. These involved the following four expedited pathways: Fast Track, Breakthrough, Priority Review, and Accelerated Approval.

Fast Track

Fourteen of the 2015 novel drugs (31%) were designated by CDER as Fast Track, meaning drugs with the potential to address unmet medical needs. Fast Track speeds new drug development and review, for instance, by increasing the level of communication FDA allocates to drug developers and by enabling CDER to review portions of a drug application ahead of the submission of the complete application.

Breakthrough

CDER designated ten of the 2015 novel drugs (22%) as Breakthrough therapies, meaning drugs with preliminary clinical evidence demonstrating that the drug may result in substantial improvement on at least one clinically significant endpoint (i.e., study result) over other available therapies. A breakthrough therapy designation includes all of the Fast Track program features, as well as more intensive FDA guidance on an efficient drug development program. Breakthrough status is designed to help shorten the development time of a potential new therapy.

Priority Review

Twenty-four of the 2015 novel drugs (53%) were designated Priority Review, in which CDER determined that the drug could potentially provide a significant advance in medical care and set a target to review the drug within six months instead of the standard 10 months.*

*In some instances, priority review is assigned as a result of the sponsor redeeming a voucher for priority review under CDER’s Priority Review Voucher program, which may mean the drug does not potentially provide a significant advance. Such drugs are not included in the list above.

Accelerated Approval

CDER approved six of the 2015 novel drugs (13%) under FDA’s Accelerated Approval program, which allows early approval of a drug for a serious or life-threatening illness that offers a benefit over current treatments. This approval is based on a “surrogate endpoint” (e.g., a laboratory measure) or other clinical measure that we consider reasonably likely to predict a clinical benefit of the drug. Once Accelerated Approval is granted, the drug must undergo additional testing to confirm that benefit; this speeds the availability of the drug to patients who need it.

Alecensa, Darzalex, Farydak, Ibrance, Tagrisso, Praxbind

Overall use of expedited development and review methods

Twenty-seven of the 2015 novel drugs (60%) were designated in one or more expedited categories of Fast Track, Breakthrough, Priority Review, and/or Accelerated Approval. Each of these designations helps expedite the speed of the development and/or approval process and is designed to help bring important medications to the market as quickly as possible.

Qualified Infectious Disease Program Designations

The Generating Antibiotics Incentives Now Act (GAIN Act) provides incentives to help bring new antibiotics and other antimicrobials to market. A drug with particular promise can be designated as a Qualified Infectious Disease Product (QIDP) by authority of the GAIN Act. In 2015, CDER approved two novel drugs with this designation.

PREDICTABILITY

PDUFA Goals Met

Under the Prescription Drug User Fee Act (PDUFA), sponsors are assessed user fees that provide FDA with the additional resources needed to meet performance goals. Throughout the year, CDER was able to meet or exceed most PDUFA goal dates for application review, agreed to with the pharmaceutical industry and approved by Congress. In 2015, CDER met its PDUFA goal dates for 96% of the novel drugs approved (43 of 45).

In 2015, CDER met its PDUFA goals for 96% of the novel drugs approved in 2015

ACCESS

First Cycle Approval

CDER approved most of the novel drugs of 2015 (39 of 45, 87%) on the “first cycle” of review, meaning without requests for additional information that would delay approval and lead to another cycle of review.

Approval in the U.S. Before Other Countries

Comparing approval to other countries offers another measure of approval efficiency. Although regulatory processes differ widely between FDA and those of regulatory agencies in other countries, about two-thirds of the novel drugs approved in 2015 (29 of 45, 64%) were approved in the United States before receiving approval in any other country.

OVERVIEW

This document represents a broad overview of CDER approvals of novel drugs for calendar year 2015.

A continuing upward trend for the annual number of CDER’s novel drug approvals necessarily relies on a corresponding increase in the number of drug applications submitted for approval. During the past decade, submissions of applications for NMEs and novel BLAs by the pharmaceutical and biotechnology industry have remained relatively stable.

More important than the quantity of novel drugs approved in 2015 are the qualities of the new drugs the pharmaceutical industry has developed and the important new roles these drugs are serving to advance medical care.

Also noteworthy is the efficiency with which most of these drugs were reviewed and approved. CDER used a variety of expedited development and review regulatory tools in an effort to help speed these drugs to market.

In all cases, while striving for efficiency of review and approval of applications for new drugs, CDER maintains its rigorous standards for demonstration of effectiveness and safety in the process.

More important than the quantity of novel drugs approved by CDER in 2015 is their quality and the important new roles they are serving to advance medical care.

Drug Designation Summary

First-in-ClassDrugs with a new and unique mechanism for treating a medical condition

Orphan DrugsDrugs approved for small populations of patients with rare diseases

BreakthroughA drug with preliminary clinical evidence demonstrating that it may result in substantial improvement on at least one clinically significant endpoint over available therapies.

Fast TrackDrugs that can treat unmet medical needs

Priority ReviewA drug is given a priority review if there is potential to provide a significant advance in existing medical care. Drugs assigned priority review under CDER’s Priority Review Voucher program are not included in this summary.

Accelerated ApprovalEarly approval based on markers that predict a reasonable benefit, with more testing to confirm clinical benefit after approval

First CycleDrugs that were approved without request for additional information that could delay approval and lead to another cycle of review

First Approved in U.S.Drugs that were approved in the United States before approval in other country

Qualified Infectious Disease Program DesignationA drug with particular promise can be designated as a Qualified Infectious Disease Product (QIDP) by authority of the Generating Antibiotics Incentives Now Act (GAIN Act)